SNi

Lore & Background

A typical representative organic reaction displaying this mechanism is the chlorination of alcohols with thionyl chloride, or the decomposition of alkyl chloroformates, the main feature being retention of stereochemical configuration. Mechanistic and kinetic studies were reported few years later by various researchers.

Reader's Guide

The SNi mechanism is significant because it explains how certain nucleophilic substitutions can occur with retention of configuration, in contrast to the inversion typically seen in SN2 reactions or racemization in SN1 reactions. Thionyl chloride first reacts with the alcohol to form an alkyl chloro sulfite, forming an intimate ion pair. The second step is the loss of a sulfur dioxide molecule and its replacement by the chloride attached to the sulphite group. The difference between SN1 and SNi is that the ion pair is not completely dissociated, so no real carbocation is formed, which would otherwise lead to racemization. This reaction type is linked to many forms of neighbouring group participation, such as the reaction of the sulfur or nitrogen lone pair in sulfur mustard or nitrogen mustard to form the cationic intermediate. The mechanism is supported by the observation that addition of pyridine leads to inversion, as pyridine reacts with the intermediate sulfite replacing chlorine, forcing the dislodged chlorine to attack from the rear. In the complete picture, the sulfite reacts with a chlorine ion in a standard SN2 reaction with inversion; when the solvent is also a nucleophile such as dioxane, two successive SN2 reactions take place and the stereochemistry is again retention. Under standard SN1 reaction conditions, the outcome is retention via a competing SNi mechanism, not racemization.

Did You Know?

• A typical example is the chlorination of alcohols with thionyl chloride, which shows retention of configuration.
• Addition of pyridine to the reaction leads to inversion of configuration.
• The mechanism involves an intimate ion pair that does not fully dissociate into a free carbocation.